“Neural Circuit Mechanisms Underlying Behavioral State Changes in Females”
Abstract: Behaviors are linked to the internal physiological states. In many species, including humans, females dramatically change their behaviors along with the state of ovulation. Abnormal forms of such behavioral changes are linked to women specific symptoms such as premenstrual syndrome. Therefore it is important to understand neural mechanisms underlying behavioral changes in females. Females of many species including mice are sexually receptive exclusively during the estrus, ovulatory phase of the estrous cycle, while they are not receptive during other phases. Sex hormones such as estrogen and progesterone are required for both ovulation and female mating behavior. Although central and peripheral mechanisms of ovulation is well characterized, neural circuit mechanisms underlying the estrus-associated change of the behavior is poorly understood. We have previously shown that progesterone receptor (PR) expressing neurons in the ventromedial hypothalamus (VMH) are essential for female mating behavior via chronic ablation of PR+ VMH neurons. However, whether PR+ VMH neurons play a role in the cyclic change of female mating behavior is unclear. We examined whether PR+ VMH neurons play a role in the estrus-associated change of female mating behavior. We find that PR+ VMH neurons strengthen their functional connections during estrus with the anteroventral periventricular nucleus, depending on estrogen signaling in PR+ VMH neurons. We further find that these projections are essential for female mating behavior during estrus. These findings demonstrate that periodic remodeling in this behaviorally salient connections plays a critical role in associating female mating behavior with an internal physiological state. We further identified a transcriptomically-defined homogeneous population expressing Cholecystokinin A receptor (Cckar) within the PR+ VMH population. The Cckar+ VMH neurons are the only neurons within the PR+ VMH neurons that regulate female mating behavior. I will present these and recent findings and future directions to discuss neural circuit mechanisms that control behavioral state changes in females.
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